An Alkaline Phosphatase-Responsive Aggregation-Induced Emission Photosensitizer for Selective Imaging and Photodynamic Therapy of Cancer Cells

Abstract

Fluorescence-guided photodynamic therapy (PDT) has been considered as an emerging strategy for precise cancer treatment by making use of photosensitizers (PSs) with reactive oxygen species (ROS) generation. Some efficient PSs have been reported in recent years, but multifunctional PSs that are responsive to cancer-specific biomarkers are rarely reported. In this study, we introduced a phosphate group as a cancer-specific biomarker of alkaline phosphatase (ALP) on a PS with the features of aggregation-induced emission (AIE) for cancer cell imaging and therapy. In cancer cells with high ALP expression, the phosphate group on the AIE probe is selectively hydrolyzed by ALP. Consequently, the hydrophobic probe residue is aggregated in aqueous media and gives a “turn on” fluorescent response. Moreover, fluorescence-guided PDT was realized by the aggregates of probe residue with strong ROS generation efficiency under white light irradiation. Overall, this work presents a strategy of applying ALP-responsive AIE PS for specific imaging cancer cells and succeeding with specific PDT upon the cancer biomarker stimulated responsive reactions.

Theranostic Fluorescent Probes

“…313,314 Very recently, Tang and He et al developed an ALP-activated AIE PS, 133P, which employs a triphenylamine derivative as the PS core and a phosphate group as an enzyme-labile moiety, respectively (Figure 72), to specifically target and kill the ALP-overexpressed cancer cells. 406 Probe 133P was nonemissive in aqueous solutions, while upon the addition of ALP its phosphate group can be efficiently hydrolyzed to obtain 133, which further formed aggregates and emitted a yellow-colored fluorescence (λ em = 540 nm). The specific fluorescent response to the presence of the ALP enzyme enabled 133P to discriminate cancer cells from normal cells and to quantify the ALP level in the cells, as a function of the fluorescence intensity.…”

“…So far, AIEgen-based-activatable fluorescent probes have been widely investigated for many biomedical applications. , Very recently, Tang and He et al. developed an ALP-activated AIE PS, 133P , which employs a triphenylamine derivative as the PS core and a phosphate group as an enzyme-labile moiety, respectively (Figure ), to specifically target and kill the ALP-overexpressed cancer cells . Probe 133P was nonemissive in aqueous solutions, while upon the addition of ALP its phosphate group can be efficiently hydrolyzed to obtain 133 , which further formed aggregates and emitted a yellow-colored fluorescence (λ em = 540 nm).…”

Dual-Functional AIE Fluorescent Probe for Visualization of Lipid Droplets and Photodynamic Therapy of Cancer

“…26−29 Conversely, luminogens with aggregationinduced emission (AIE) performance could effectively produce ROS even in the aggregated status and circumvent the ACQ effect. 30,31 These aggregation-induced emission luminogens (AIEgens) would undoubtedly be satisfactory candidates for PDT. Therefore, the development of biomarker-responsive AIE fluorescent probes accompanied by PDT function has attracted more and more attention.…”

Construction of supramolecular dimer photosensitizers based on triphenylamine derivatives and cucurbit[8]uril for photocatalysis

“…As a classic AIE group, photosensitizers based on triphenylamine and its derivatives have been widely reported in the field of photodynamic therapy due to their excellent ROS generating ability. 34–39 However, their application in the construction of supramolecular assembly photosensitizers and photocatalysis has been rarely studied. In this work, we designed and synthesized two triphenylamine derivatives (MATM and MeOTPPy) with a typical D–A configuration and D–π–A configuration, which not only have good water solubility, but also have excellent AIE luminescence performance.…”